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Donatella Fedeli, Maura Montani, Laura Bordoni, Roberta Galeazzi, Cinzia Nasuti, Luísa Correia-Sá, Valentina F Domingues, Maini Jayant, Vani Brahmachari, Luca Massaccesi, Emiliano Laudadio, Rosita Gabbianelli
The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels...
November 5, 2016: Neuroscience
Jin-Il Kim, Seong Gak Jeon, Kyoung Ah Kim, Yong Jun Kim, Eun Ji Song, Junghyun Choi, Kyu Jeung Ahn, Chong-Jin Kim, Ho Yeon Chung, Minho Moon, Hyunju Chung
The nuclear receptor related-1 (Nurr1) protein plays an important role in both the development of neural precursor cells (NPCs) and cognitive functions. Despite its relevance, the effects of Nurr1 on adult hippocampal neurogenesis have not been thoroughly investigated. Here we used RT-PCR, western blot, and immunocytochemistry to show that adult hippocampal NPCs abundantly express Nurr1. We then examined the effect of Nurr1 activation on adult hippocampal NPCs using amodiaquine (AQ), an anti-malarial drug that was recently discovered to be a Nurr1 agonist...
September 28, 2016: Stem Cell Research
Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
October 25, 2016: Archives of Pharmacal Research
Yeomoon Sim, Gunhyuk Park, Hyeyoon Eo, Eugene Huh, Pil Sung Gu, Seon-Pyo Hong, Youngmi Kim Pak, Myung Sook Oh
Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)...
October 19, 2016: Neuroscience
Wang Yan, Zhao-Ying Chen, Jia-Qi Chen, Hui-Min Chen
BACKGROUND: Neural stem cells (NSCs) are pluripotent and self-renewing cells which could differentiate into diverse types of neural cells, such as dopaminergic (DA) neurons, the loss of which is the typical characteristic of Parkinson's disease (PD). This study aimed to examine the molecular mechanisms of BMP2-mediating NSCs differentiation into DA neurons. METHODS: Different concentrations of BMP2 were used to induce the differentiation of NSCs into DA neurons, which were characterized by the number and the neurite lengths of tyrosine hydroxylase (TH)+ and dopamine transporter (DAT)+ neurons by immunocytochemistry...
2016: American Journal of Translational Research
D J Vidyadhara, H Yarreiphang, T R Raju, Phalguni Anand Alladi
Disease genetics in admixed populations like Hispanic-Americans, African-Americans, etc. are gaining importance due to high disease burden in them. Furthermore, epidemiological studies conclusively prove ethnicity-based differential prevalence of Parkinson's disease (PD), since the American-Caucasians are more susceptible than Asian-Indians and Africans. Contradictorily, Anglo-Indians, an admixture of Europeans and Asian-Indians are five-times less susceptible than Indians. We evaluated the neural basis of this phenomenon using the cytomorphological features of susceptibility to nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
October 4, 2016: Molecular Neurobiology
Cristian Arredondo, Marcela González, María Estela Andrés, Katia Gysling
Dopamine neurons are overstimulated by drugs of abuse and suffer molecular alterations that lead to addiction behavior. Nurr1 is a transcription factor crucial for dopamine neurons survival and dopamine production, activating the transcription of key genes like tyrosine hydroxylase (TH). Interestingly, nuclear factor-kappa B (NF-κB) has emerged as a new Nurr1 partner in response to inflammatory stimulus. In this study we evaluated the effects of single and repeated amphetamine administration in the expression of Nurr1 and the NF-κB p65 subunit in the rat ventral tegmental area (VTA)...
September 26, 2016: Brain Research
Pengguo Chen, Jie Li, Yan Huo, Jin Lu, Lili Wan, Quanjun Yang, Jinlu Huang, Run Gan, Cheng Guo
Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor. It participates in regulating cell differentiation, proliferation and apoptosis. We previously demonstrated that NR4A2 expression in fibrotic liver reduced significantly compared with normal liver and NR4A2 knockout in HSCs promoted ECM production...
2016: Scientific Reports
Guo Zu, Jihong Yao, Anlong Ji, Shili Ning, Fuwen Luo, Zhenlu Li, Dongcheng Feng, Yiqi Rui, Yang Li, Guangzhi Wang, Xiaofeng Tian
: Intestinal ischemia/reperfusion (I/R) injury is a potentially life-threatening condition that can cause injuries to remote organs at the end stage. The damage caused by intestinal I/R insult induces changes in the barrier functions of the intestine, and the intrinsic mechanism of regeneration is often insufficient to restore barrier functions, as indicated by the high mortality rate of patients experiencing intestinal I/R injury. However, little is known about the mechanisms of intestinal regeneration after I/R injury...
August 24, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Yang Sheng, Emily Filichia, Elizabeth Shick, Kenzie L Preston, Karran A Phillips, Leslie Cooperman, Zhicheng Lin, Paul Tesar, Barry Hoffer, Yu Luo
INTRODUCTION: The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. METHODS: In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3)...
August 2016: Brain and Behavior
Scott W Lallier, Amanda E Graf, Gavisha R Waidyarante, Lynette K Rogers
Advances in neonatal care have allowed premature infants to survive at earlier gestational ages, but they are often afflicted with neurological delays or deficits. Maternal inflammation has been identified as a major risk factor for premature birth and once born, infants often require supplemental oxygen for survival. Nurr1 (NR4A2) is an orphan nuclear receptor with no known binding site and is essential for the growth of midbrain dopamine neurons. Others have reported that Nurr1 can act as an anti-inflammatory transcription factor in microglia and astrocytes and respond lipopolysaccharide (LPS)...
October 19, 2016: Neuroreport
Jia Yu, Xueting Li, Junwei Yang, Yanping Wu, Baixiang Li
BACKGROUND Simazine is a triazine herbicide used worldwide in both agricultural and non-agricultural fields that is frequently detected in surface water and groundwater. Due to its widespread use, an increasing amount of research has focused on the potentially serious environmental and health risks. MATERIAL AND METHODS We used Western blotting and real-time quantitative PCR to analyze the effects of simazine on dopamine neuronal development-related factors in MN9D dopaminergic cells. RESULTS The expression of tyrosine hydroxylase (TH) mRNA was significantly increased after treatment with 300 and 600 μmol L-1 simazine after 24 and 48 h...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Lu Gao, Wenbo Zhou, Breanna Symmes, Curt R Freed
Parkinson's disease is characterized by the death of dopaminergic neurons in the substantia nigra. To understand the molecular mechanisms of the disease, an in vitro model is important. In the 1990s, we used the SV40 large T antigen to immortalize dopaminergic neurons derived from Embryonic Day 14 rat mesencephalon. We selected a clone for its high expression of dopaminergic neuron markers such as tyrosine hydroxylase (TH), and we named it 1RB3AN27 (N27). Because the original N27 cell line has been passaged many times, the line has become a mixture of cell types with highly variable expression of TH...
2016: PloS One
Mohammad Jodeiri Farshbaf, Mahboobeh Forouzanfar, Kamran Ghaedi, Abbas Kiani-Esfahani, Maryam Peymani, Alireza Shoaraye Nejati, Tayebeh Izadi, Khadijeh Karbalaie, Maryam Noorbakhshnia, Soheila Rahgozar, Hossein Baharvand, Mohammad Hossein Nasr-Esfahani
Parkinson's disease (PD) can degenerate dopaminergic (DA) neurons in midbrain, substantia-nigra pars compacta. Alleviation of its symptoms and protection of normal neurons against degeneration are the main aspects of researches to establish novel therapeutic strategies. PPARγ as a member of PPARs have shown neuroprotection in a number of neurodegenerative disorders such as Alzheimer's disease and PD. Nuclear receptor related 1 protein (Nurr1) is, respectively, member of NR4A family and has received great attentions as potential target for development, maintenance, and survival of DA neurons...
September 2016: Molecular and Cellular Biochemistry
Yinxiu Ding, Zixin Zhang, Jiangbo Ma, Hechun Xia, Yin Wang, Yinming Liu, Quanrui Ma, Tao Sun, Juan Liu
Parkinson's disease (PD) is a severe neurodegenerative disorder. Although the detailed underlying molecular mechanism remains to be elucidated, the major pathological feature of PD is the loss of dopaminergic (DA) neurons of the substantia nigra. The use of donor stem cells to replace DA neurons may be a key breakthrough in the treatment of PD. In the present study, the growth kinetics of hippocampal neural stem cells (Hip‑NSCs) isolated from postnatal mice and cultured in vitro were observed, specifically the generation of cells expressing DA neuronal markers nuclear receptor related‑1 protein (Nurr1) and tyrosine hydroxylase (TH)...
September 2016: Molecular Medicine Reports
Mohammad Reza Ashraghi, Gennaro Pagano, Sotirios Polychronis, Flavia Niccolini, Marios Politis
BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulin-resistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment...
June 30, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Douglas A Grow, DeNard V Simmons, Jorge A Gomez, Matthew J Wanat, John R McCarrey, Carlos A Paladini, Christopher S Navara
UNLABELLED: : The progressive death of dopamine producing neurons in the substantia nigra pars compacta is the principal cause of symptoms of Parkinson's disease (PD). Stem cells have potential therapeutic use in replacing these cells and restoring function. To facilitate development of this approach, we sought to establish a preclinical model based on a large nonhuman primate for testing the efficacy and safety of stem cell-based transplantation. To this end, we differentiated baboon fibroblast-derived induced pluripotent stem cells (biPSCs) into dopaminergic neurons with the application of specific morphogens and growth factors...
September 2016: Stem Cells Translational Medicine
Baek-Soo Han, Kyoung-Shim Kim, Yu Jin Kim, Hoe-Yune Jung, Young-Mi Kang, Kyu-Suk Lee, Mi-Jin Sohn, Chun-Hyung Kim, Kwang-Soo Kim, Won-Gon Kim
Nurr1 is an orphan nuclear receptor that is essential for the differentiation and maintenance of dopaminergic neurons in the brain, and it is a therapeutic target for Parkinson's disease (PD). During the screening for Nurr1 activators from natural sources using cell-based assay systems, a methanol extract of the combined stems and roots of Daphne genkwa was found to activate the transcriptional function of Nurr1 at a concentration of 3 μg/mL. The active components were isolated and identified as genkwanine N (1) and yuanhuacin (2)...
June 24, 2016: Journal of Natural Products
Olga Gorelenkova Miller, Jessica B Behring, Sandra L Siedlak, Sirui Jiang, Reiko Matsui, Markus M Bachschmid, Xiongwei Zhu, John J Mieyal
AIMS: Neuroinflammation and redox dysfunction are recognized factors in Parkinson's disease (PD) pathogenesis; and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. Here we investigated the potential impact of Grx1 upregulation in the CNS on dopaminergic viability. RESULTS: Increased GLRX copy number in PD patients was associated with earlier PD onset; and Grx1 levels correlated with levels of pro-inflammatory TNF-α in mouse and human brain samples, prompting mechanistic in vitro studies...
May 25, 2016: Antioxidants & Redox Signaling
Pedro Montes, Elizabeth Ruiz-Sánchez, Minerva Calvillo, Patricia Rojas
Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age...
September 2016: Stress: the International Journal on the Biology of Stress
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